4,4'‑Bond secalonic acid D targets SP cells and inhibits metastasis in hepatocellular carcinoma

Chen,Li; Cheng,Miao‑Miao; Li,Ya‑Ping; Lin,Shao‑Feng; Zheng,Qiu‑Hong; Liu,Qin‑Ying

doi:10.3892/mmr.2020.11055

4,4'‑Bond secalonic acid D targets SP cells and inhibits metastasis in hepatocellular carcinoma

Authors:
- Li Chen
- Miao‑Miao Cheng
- Ya‑Ping Li
- Shao‑Feng Lin
- Qiu‑Hong Zheng
- Qin‑Ying Liu
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Affiliations: Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, Fujian 350014, P.R. China, Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou, Fujian 350002, P.R. China
Published online on: April 6, 2020 https://doi.org/10.3892/mmr.2020.11055
Pages: 2624-2632

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Abstract

The existence of cancer stem cells (CSCs) is considered to be the main reason for chemoresistance, metastasis and the ultimate failure of treatment in hepatocellular carcinoma (HCC). However, there are a few chemical agents that may inhibit CSCs. The present study identified that 4,4'‑bond secalonic acid D (4,4'‑SAD), a compound isolated from the marine‑derived fungus Penicillium oxalicum, inhibited the growth of side population (SP) cells isolated from human liver cancer cell lines PLC/PRF/5 and HuH‑7 by attenuating the expression of ATP‑binding cassette superfamily G member 2. Furthermore, the results of wound healing, Transwell, western blotting and reverse transcription‑quantitative PCR assays demonstrated that 4,4'‑SAD suppressed the invasion and migration of SP cells by downregulating matrix metallopeptidase 9 (MMP‑9) and upregulating the antagonist tissue inhibitor of metalloproteinases 1 in vitro. Moreover, in vivo study results found that 4,4'‑SAD had anti‑lung metastasis efficacy via the decrease of MMP‑9 expression in the H22 HCC model of Kunming mice. Therefore, the present study identified the potential of 4,4'‑SAD as a promising candidate for the treatment of advanced liver cancer.

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